Stem cell based therapies for ameliorating radiation-induced cognitive dysfunction in a pediatric model of medulloblastoma

Radiotherapy is a front line treatment used for the treatment of medulloblastoma, a common CNS tumor in children. Cranial irradiation remains the only treatment capable of successfully forestalling the growth of this brain tumor, and is largely responsible for the long-term survival of children so afflicted. While cranial radiotherapy is an effective treatment for CNS cancer, it is frequently associated with debilitating and progressive cognitive impairment. Depending on the extent of the initial disease, patient age, and radiation dose, marked reductions in IQ (i.e. up to 10-20 points) are routinely observed that adversely impact quality of life. Radiation-induced cognitive dysfunction is a growing problem, in part, due to increasing cancer survival rates and because there are no satisfactory long-term solutions to this unmet medical need.
To address this serious clinical problem, we propose to test 2 development candidates for their capability to ameliorate radiation-induced cognitive dysfunction. Rodents subjected to head-only irradiation will be cranially transplanted with our selected stem cell derivative disease candidates and tested for improved cognitive performance 1 and 4 months later. Our past findings showing that stem cell transplants into the brain can reverse the adverse effects of irradiation on cognitive performance suggest that such an approach may one day help cancer survivors suffering from their deteriorating mental health.

Statement of Benefit to California:

Radiotherapy is a front line treatment used throughout the world and in California for the treatment of a variety of CNS malignancies. It remains the only treatment capable of successfully forestalling the growth of brain tumors, and is largely responsible for the long-term survival of children afflicted with medulloblastoma. While cranial radiotherapy is an effective treatment for CNS cancer, it is frequently associated with debilitating and progressive cognitive impairment. Cognitive dysfunction is a growing problem, in part, due to increasing survival rates among all cancer patients, including pediatric cases, but also since there are no satisfactory long-term solutions to this unmet medical need. Therefore, successful development of a stem cell based treatment for the reversal of radiation-induced cognitive dysfunction would benefit California in several major ways. First, academic and private sector personnel employed in California involved in the preclinical studies necessary to demonstrate efficacy and safety of the stem cell treatments would provide direct economic stimulus. Second, the state of California would be well positioned to attract cancer patients throughout the United States, and possibly the world, thereby benefiting from the increased economic activity associated with a rise in clinical trials. Lastly, success of CIRM funded research may stimulate philanthropic efforts aimed at promoting stem cell based research in California.